Design and synthesis of novel spin-labeled camptothecin derivatives as potent cytotoxic agents

Bioorg Med Chem. 2014 Nov 15;22(22):6453-8. doi: 10.1016/j.bmc.2014.09.035. Epub 2014 Sep 28.

Abstract

In our continuing search for natural product-based spin-labeled antitumor drugs, 20 novel spin-labeled camptothecin derivatives were synthesized via a Cu-catalyzed one pot reaction and evaluated for cytotoxicity against four human tumor cell lines (A-549, MDA-MB-231, KB, and KBvin). Eighteen of the target compounds (9a, 9b, 9d-9k, 9m-9t) exhibited significant in vitro antiproliferative activity against these four tested tumor cell lines. Compounds 9e and 9j (IC50 0.057 and 0.072μM, respectively) displayed the greatest cytotoxicity against the multidrug-resistant (MDR) KBvin cell line and merit further development into preclinical and clinical drug candidates for treating cancer including MDR phenotype.

Keywords: C-20 position; Camptothecin; Cytotoxic activity; Spin-labeled.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / toxicity
  • Camptothecin / chemical synthesis
  • Camptothecin / chemistry*
  • Camptothecin / toxicity
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Humans
  • KB Cells
  • Spin Labels
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Spin Labels
  • Camptothecin